This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives

Over the past years, there has been a growing number of knee osteoarthritis (KOA)
patients who are not willing to comply with long-term non-steroidal anti-inflammatory
drugs (NSAID) treatment and wish to use herbal anti- rheumatic medicine. This study
assessed the clinical effects of Garcinia kola (GK) in KOA patients.

Patients and methods

Prospective randomized, placebo controlled, double blind, clinical trial approved
by the institutional medical ethics review board and written informed consent obtained
from each patient. All KOA patients presenting at the Obafemi Awolowo University Teaching
Hospital complex were recruited into the study. The patients were grouped into four
(A = Placebo, B = Naproxen, C = Garcinia kola, D = Celebrex). The drugs and placebo were given twice a day per oral route. Each
dose consisted of 200 mg of G. kola, Naproxen (500 mg), Celebrex (200 mg) and Ascorbic acid (100 mg). The primary outcome
measure over six weeks study period was the change in mean WOMAC pain visual analogue
scales (VAS). Secondary outcome measures included the mean change in joint stiffness
and physical function (mobility/walking).

Results

143 patients were recruited, 84 (58.7%, males – 24, females – 60) satisfied the selection
criteria and completed the study. The effect of knee osteoarthritis bilateralism among
the subjects was not significant on their outcome (p > 0.05). The change in the mean
WOMAC pain VAS after six weeks of G. kola was significantly reduced compared to the placebo (p < 0.001). Multiple comparisons
of the mean VAS pain change of G. kola group was not lowered significantly against the naproxen and celebrex groups (p >
0.05). The onset of G. kola symptomatic pain relief was faster than the placebo (p < 0.001). However, it was slower
than the active comparators (p > 0.05). The duration of therapeutic effect of Garcinia kola was longer than the placebo (p > 0.001). G. kola period of effect was less than naproxen and celebrex (p < 0.001). G. kola subjects had improved mean change mobility/walking after six weeks better than the
control group(p < 0.001). The mean change in mobility of the G. kola group when compared to the active comparators was not significantly better (p < 0.05).
The mean change of knee joint stiffness (p < 0.001) and the change of mean WOMAC score
(p < 0.001) were improved on Garcinia kola as compared to the placebo. The mid term outcome of eleven Garcinia kola subjects after cessation of use had a mean pain relief period of 17.27 +/- 5.15 days
(range: 9–26 days). There was no significant cardiovascular, renal or drug induced
adverse reaction to Garcinia kola.

Conclusion

Garcinia kola appeared to have clinically significant analgesic/anti-inflammatory effects in knee
osteoarthritis patients. Garcinia kola is a potential osteoarthritis disease activity modifier with good mid term outcome.
Further studies are required for standardization of dosages and to determine long-term
effects.

Background

Osteoarthritis is the most common form of joint disease, affecting the knee more than
other joints [1]. Several factors play a role in osteoarthritis risk; these include age, gender, genetics,
behavioral influences and ethnicity [2]. Trauma is a recognized predisposing factor to development of osteoarthritis of the
knee (KOA) associated with raised intra osseous pressure and death of the chondrocytes.
Osteoarthritis of the knees reduces the ability to avoid obstacles and supporting
epidemiologic studies have found osteoarthritis to be a risk factor for falls [3]. The pain associated with osteoarthritis of the knees increased the propensity to
trip on an obstacle and underscores the importance of treating pain associated with
osteoarthritis [3].

As the population ages or the disease worsens, knee osteoarthritis is associated with
incapacity and a deteriorating quality of life owing to increased pain, loss of mobility,
and the consequent loss of functional independence [4]. There is general increase in life expectancy with increasing involvement of the
younger age group in foot ball, road traffic injuries, political/communal wars and
disaster. It means that increasing numbers of people will present with reduced quality
of life associated knee osteoarthritis. As a result, osteoarthritis is often treated
by medical or surgical intervention. Pain relief is therefore a fundamental aspect
in dealing with this illness.

In patients in whom pharmacological treatment is ineffective, who are not candidates
for surgery (or who reject it); other pain and predisposing factors management procedures
should be considered [5]. Drug therapy of osteoarthritis is empirical and largely directed towards providing
symptomatic relief, primarily by the use of analgesics and non-steroidal anti-inflammatory
drugs (NSAIDs). Over the past years, there are a growing number of younger age group
patients with KOA patients who are not willing to comply with long term NSAIDs treatment
and who wish to use more naturally occurring ant rheumatic medicine.

Garcinia kola Heckel of the family Guttiferaceae [6] is called Kola bitter, Bitter Kola, False or Male Kola. The Nigerian names are Adu,
Ugolu in Ibo language; Orogbo in Yoruba; and Akan in Tweapia language. The constituents
include- Flavinoids (bioflavonoid), xanthenes and benzophenones. It has shown anti-inflammatory,
ant parasitic, antimicrobial and antiviral properties [[7-12], and [13]].

The pharmacodynamic mechanism of Garcinia kola action is anchored on Kolaviron (KV) [[14-17], and [18]]. Garcinia kola acts by restoring and maintaining the balance of fatty acids in osteoarthritis. It
causes balanced inhibition of metabolism in the cyclo oxgenase pathway (COX-1 and
COX-2). It inhibits amino acid metabolism by the 5-lipoxygenase (5-LOX) enzymes. Therefore
the normal physiologic organ functions are maintained. The inhibition of 5-LOX result
into reduction in the production of leukotrienes (LTB4), an agent that do enhance
white blood cell chemo taxis and the subsequent release of histamines, reactive oxygen
species and pro-inflammatory cytokines. Garcinia kola has a strong antioxidant effect which limits the oxidative conversion of amino acid
by reactive oxygen species to other damaging fatty acid products [19]. Kolaviron exerts a hypocholesterolaemic effect which illustrate the anti-atherogenic
property of G. kola [20]. The excretion has neither organ nor behavioral abnormalities. Blood electrolytes
were unchanged and liver enzymes and markers of renal function were all within normal
limits [14,16].

Safety of the food effects

Garcinia kola is safe taken with or without other foods. Taking it an hour before or after meals
may help to increase the absorption of the key ingredients. Food does not affect the
metabolism of G. kola and may buffer effects of mild indigestion [17]. Garcinia kola is primarily carried bound to albumin in the blood and only a minor amount is metabolized
by hepatic metabolism [18]. Kolaviron does not affect phase 1 drug metabolizing enzymes [16] but induce phase 2 enzymes [21]. It may be classified as a bifunctional inducer according to the classification of
Greenwald et al 1995 [22].

Drug interactions of Kolaviron have been shown to be hepatoprotective [[7,10,21,23,24], and [25]]. It does not appear to have a pronounced effect on drug metabolizing enzymes [21] and no known interactions with orthodox medications [26]. The tablet properties could be controlled to obtain optimal release of the bioactive
compounds [27].

Although surgery can relieve the pain of KOA and restore function, not all patients
are candidates for surgery, and many want to avoid or delay it if possible. Therefore,
alternative treatments are important [28] which could include G. kola that have not been evaluated for knee osteoarthritis. To date, there is no clinical
documentation of the effect of G. kola on the knee osteoarthritis through a Medline search and locally available literatures.
The research hypothesis was that G. kola have a positive effect on knee osteoarthritis as depicted in Yoruba folk songs. The
objective of the study was to evaluate the clinical effects of G kola on knee osteoarthritis
pain, stiffness and function. The effects of G. kola in KOA is been investigated in Nigerians through a multidisciplinary research study
group based at the Obafemi Awolowo University, Ile-Ife, Osun State; Nigeria.

Methods

Inclusion criteria

Men and women between the ages of 18 and 80 years were enlisted if they had knee trauma
or overuse of the knees prior to the onset of symptomatic osteoarthritis. Only uncomplicated
hypertensive patients solely on Nifedipine were included. Within the routine clinical
practice, many of our confirmed KOA patients do present with hypertensive heart disease
on multiple therapies. Basically our research center is in resource constrained country
where high technology laboratory support needed to identify specific adverse drug
interactions that could be associated with multiple anti hypertensive medications
is not available. It was due to this peculiar limitation and the need to enhance clarity
of interpretation of subject's clinical features, study drug's efficacy and safety
assessment within available international standard facilities that necessitated the
inclusion of patients with uncomplicated hypertensive solely on Nifedipine.

Patient's diets were not altered from their pre study period. The other inclusion
criteria in the study were – osteoarthritis of the knee verified according to the
clinical, laboratory, radiographic criteria of the American College of Rheumatology
(ACR) and resting visual analog scale pain intensity in the target knee > 45 mm.

Exclusion criteria

Patients with known allergic reactions (to Garcinia kola, celebrex and naproxen); Kidney failure (blood creatinine > 84 umol/L); abnormal
liver function (SGOT > 35 U/L or SGPT > 35 U/L or GGT > 50 U/L); gastrointestinal
ulcers (bleeding or discolored stool during the past 8 weeks); malignant diseases;
systemic therapy with corticosteroids during the past 8 weeks; surgery of the test
joint during the past 8 weeks; inflammatory joint diseases(ESR > 40 mm/h);chronic
heart failure (NYHA grade III or IV); Chronic obstructive airway disease requiring
prophylactic medication and participation on a clinical trial during the past 4 weeks.
Patients with absolute indication for surgery and knee instability were excluded.
Subjects with high levels of clinical disability (> 34 on the WOMAC scale) were excluded
as it was unlikely that they could perform the experimental protocol consistently.
Also the knee requiring no weight bearing and who had intra-articular injections into
the study joint within 3 months prior to first visit were excluded. No herbal or allopathic
treatment, which could influence the outcome of the study, was permitted during the
course of the study. Crossing over of patients from one subgroup to another was excluded
through surveillance.

Settings

Subjects were recruited into the study between February 20th, 2004 and August 19th, 2006 at the orthopedics and general outpatient's clinics of the Obafemi Awolowo
University Teaching Hospital Complex, Ile-Ife (OAUTHC); Nigeria.

Study medication and blinding

At the beginning of the study, no commercial preparation of Garcinia kola was available. G. kola seeds were obtained from a market in Ile-Ife, authenticated by Mr. A.T. Oladele, the
herbarium, Department of Pharmacognosy, Obafemi Awolowo University.

G. kola 200 mg was given twice orally per day for six weeks. Active comparators were Naproxen
500 mg tablets twice daily, and Celebrex 200 mg twice daily were given orally. Placebo
study medication was ascorbic acid, 100 mg tablet given twice daily. The patient in
each group was given identical study medication of the same physical appearance aimed
at eliminating psychological effects on the subjects. The subjects have not been previously
exposed to research drug medications.

All study medications were prepared by a 10 years post-qualified nursing staff and
administered to each patient by a senior registrar in orthopedic surgery. A family
medicine physician of five year post fellowship qualification acted as a masked clinical
outcome evaluator. The voluntary nursing staff, the senior registrar and masked evaluator
were not part of the study group. The Nifedipine for hypertensive were supplied to
patients from the teaching hospital pharmacy shop to ensure uniformity of quality
control. A consultant radiologist with a neutral role status in the study screened
the plain X-ray of patients and confirmed radiological features of knee osteoarthritis.

Study design

It was a randomized, double-blind, placebo-controlled, parallel-group study trial
of the clinical effects of G. kola in knee osteoarthritis. The research medication dose assessor, clinical assessors,
subjects and orthopedic surgeons were blinded to the treatment group for the six weeks
of study. The G. kola subgroup was followed up for the midterm evaluation of therapeutic effect after the
intake was discontinued.

The study was approved by the institutional medical ethics review board and was carried
out in accordance with the ethical principles of the Declaration of Helsinki. A written
informed consent was obtained from each patient that fulfilled the inclusion criteria
before randomization.

Study randomization

To determine the presence of KOA, detailed history was obtained and clinical examination
performed. Adults were classified as having clinical knee OA by using the criteria
determined by the American College of Rheumatology (ACR) [29].

Randomization occurred in blocks of four within each stratum, using computer generated
random numbers (Excel 5.0). The patients were grouped into four (A = placebo, B =
naproxen, C = Garcinia kola, D = celebrex). Both assessors and patients were blind to the allocation and not
informed about the block size until after completion of the study. Subjects were treated
for six weeks and each of them had weekly follow-up visits until the time of study
withdrawal. Study medications were taken in the morning and at noon, half an hour
before meal times. No additional analgesics, NSAIDs or systemic corticosteroids were
allowed during the study phases.

Objectives

At all visits, the patients completed WOMAC index to assess pain, stiffness, and physical
function. The primary efficacy end point was the mean change from baseline in the
WOMAC pain subscale VAS at six weeks. Secondary outcome measures included the stiffness
and physical function.

Clinical assessments

The initial assessment (day -7) comprised of medical history, examination and WOMAC-VAS index. The "most painful knee
joint" refer to the side of knee joint with the highest VAS pain score when a subject
is having bilateral KOA. In bilateral knee OA, the side of the knee joint with the
highest VAS pain score was the primary focus of measurement for future assessment
in the study. Blood and urine samples were taken for standard laboratory tests. The
onset of therapeutic effect of the study medication as used in this study was the
mean time (minutes) recorded for the onset of KOA symptomatic reliefs. The duration
of therapeutic effect of the study medication was the mean time (minutes) recorded
for the return of KOA symptoms after a relief following study medication intake.

The radio diagnostic criterion of Kellgren and Lawrence [30]scheme was used for the knee osteoarthritis severity assessment. All patients underwent radiographic
analysis of both knee joint using Kellgren-Lawrence less or equal to grade 2 as case
definition.

The level of clinical disability was quantified by using the Western Ontario and McMaster University Osteoarthritis
(WOMAC) index [30]. Disability was assessed using the physical function section of WOMAC, which contains
17 questions relating to functional disability, scored from 0 to 4 by the subject.

At the second study visits (day 0), laboratory findings were compared with exclusion criteria and diary entries were
checked. Patients who met all study criteria filled in the WOMAC questionnaire (baseline),
received study medication and thereby entered the intent to treat population.

At the study visits on days 7,14,28,35, and 42, patients filled in WOMAC questionnaires, and compliance was checked by diary entries
and study medication. Adverse events were recorded by checking diary entries as well
as by direct questioning of the patients.

At the study visit on day 42, blood and urine samples were taken. The masked clinical outcome evaluator and consultant
orthopedic surgeon independently recorded their final overall assessment of the change
of disease activity by the study medication on 100 mm visual analogue scales (VAS).
Direct inquiry and visual inspection of the returned sachets container were used for
monitoring compliance. The osteoarthritis protocol instrument used for the study has
a section on the disease symptom/symptom description. It evaluates each subject from
the day 0 to the end of study at six weeks. The subjective response of the patients
to the questions on walking distance was distinct. They were asked if the distance
used to cover by walking has improved, or there is no change, or it deteriorated at
the end of the study compared to the day 0.

Safety

The subjects who had received at least a dose of the research medication s were assessed
for their safety. Tolerability evaluations consisted of determining clinical laboratory
test abnormalities such as hepatic (aminotransferase activities) and renal (serum
creatinine) function, adverse events, and physical examinations. Adverse events reported
by the patient or observed by the investigator during clinical evaluation were recorded.
In addition, patients were questioned at each visit regarding the occurrence of adverse
events using a nonspecific question. Investigators rated the intensity of adverse
events and their subjective assessment of the relationship to study medication while
blinded to the treatment group.

Statistical analyses

All analyses were performed on the intention to treat cohort, defined as all patients
who took at least a dose of study medications. Data were analyzed by using Statistic
Package for Social Sciences (SPSS) version 11.0 for windows. The comparability of
patients in the four treatment groups was determined from the demographic data and
baseline haemodynamic values. The change in the mean of the group and mean time of
study medications therapeutic duration were evaluated using 2-way ANOVA with Post
Hoc comparison test. The confidence interval (CI) was at 95% and the P-value was considered
significant at p ≤ 0.05.

Study limitations

Limited numbers of knee osteoarthritis patients were available for the study. Lack
of research grants to provide study medications and laboratory investigations free
for long term and to include larger groups of would be subjects at multiple centers
in Nigeria.

Results

Demographic characteristics

A total of 143 patients who had post traumatic knee osteoarthritis (unilateral = 94,
bilateral = 98) on 192 limbs were recruited. Eighty-four patients (58.7%) with KOA
in 121 limbs satisfied the selection criteria. All the patients who received at least
a dose of the research drugs had adequate documentation of their data in each subgroup
and were used for analysis. There were 24 males (28.6%) and 60 females (71.4%) with
M: F: 1:2.5. The proportion of bilateral knees involvement is shown in Table 1 which compared patients in the four treatment groups. The effect of knee osteoarthritis
bilateralism among the subjects was not significant (p > 0.913). The WOMAC score at
day 0 was not significantly different among the four study groups (p > 0.05). A clinical
photographs of typical Garcinia kola is illustrated in Figure 1. The major sources of trauma were Road Traffic Accident 46(54.8%), Sports injury
19(22.6%), Fall from height 18 (21.4%) and prolonged over use from driving long distance
for over 25 years, 1(1.2%). Knee osteoarthritis in young adults was common after sporting
knee injury and fall from height. The women often were those carried as passenger
on motor cycle before they sustained injury. The mean duration of trauma before the
onset of symptomatic knee osteoarthritis for males was 17.4 years +/- 7.3 and females
14.2 years +/- 8.6. There was 100% compliance rate in the control and celebrex groups.
A patient (4.76%) in the naproxen group was unable to come to the hospital for the
last two days evaluation due to diarrhea. He was traced home for evaluation and discovered
the medication was taken. Two patients in the Garcinia kola group stopped after completion of 39 and 40 days on the medication. It was due to
light headedness and palpitation in each of the patients. Both patients were hypertensive
before the commencement of the study. They were lost during the mid term follow up
period of the study. The data from the patients were accepted for analysis after completion
of 92.8% and 95.2% of the six weeks study period.

Clinical outcome

Analysis was restricted to eighty-four patients with adequate allocation concealment.
All the patients that received at least a dose of the study medications had adequate
documentation of their data in each subgroup. The change in the mean WOMAC pain VAS
after six weeks of G. kola was significantly reduced compared to the placebo (p < 0.001, CI:-2.01_-1.15, R2 = 0.8). Multiple comparisons of the mean of pain change in the G. kola group was not lowered significantly against the naproxen and celebrex groups (p >
0.05, CI:-0.56–0.85). There was no statistically significance between the change of
mean VAS pain reduction of the G. kola, naproxen and celebrex groups. The mean time (minutes) of onset of symptomatic pain
relief were 61.4 +/- 11.3(range: 39.0–77.2); 69.1 +/- 13.1 (range:43.2–86.3) and 55.8
+/- 8.9 (range:37.1–67.0) for the naproxen,G. kola and celebrex subgroup respectively(p > 0.05). The onset of G. kola symptomatic pain relief was faster than the placebo (p < 0.001, CI: 10.0–19.9, R2 = 0.87). However, G. kola onset of action appeared to be slower than the active comparators (p > 0.05, CI:-2.4-
9.3) as shown in Figure 2.

Figure 2.The mean time of onset of action of the study medication (minutes). The mean time (minutes) of onset of symptomatic pain relief was naproxen (61.38
+/- 11.38); G. kola (69.13 +/- 13.12) and Celebrex (55.81 +/- 8.88). The onset of G. kola symptomatic pain relief was faster as compared to the control (p < 0.001) and the
active comparators (p > 0.05) is shown in Figure 2.

After cessation of G. kola use, eight (38.1%) patients were lost to follow up at clinic due to farming/trading
activities which took them out of the study environment. The knee joint pain relief
reported by eleven (52.4%) patients that were seen at clinic lasted for a mean period
of 17.3 +/- 5.2 days (range: 9.0–26.0). There was no deterioration of the disease
symptoms. The two (9.52%) hypertensive subjects (a female senior lecturer and a male
principal nursing staff) who had an episode of dizziness and light headedness were
excluded from the mid term follow up report. The pain relief pattern post cessation
of G kola is associated with the duration of therapeutic effects (p < 0.006) as illustrated
in Figure 3.

No patient in any of the four subgroup experienced symptoms suggestive of hepatic
failure, hepatic dysfunction or renal failure. None had aminotransferase levels ≥
twice the upper limit of the reference range or serum creatinine levels ≥ 1.5 times
the upper limit of the reference range. No statistically significant differences were
observed between the groups A, B, C, and D in the proportion of patients who reported
at least one or more adverse events.

Among adverse events considered to be drug related reported by about 1% of patients
was peripheral edema 1(4.7%) in the celebrex group as compared to the placebo group.
Two patients (9.5%) in the naproxen group had an event that was considered serious
and related to the study drug: diarrhea. The side effects of G. kola included increased libido 9(42.8%), prolonged sleeping period 11 (52.4%) and weight
loss 17 (80.9%). There was no significant cardiovascular, renal or drug induced adverse
reaction to Garcinia kola as depicted in Table 2. No adverse event reported in the placebo group was considered both serious and related
to the study medication.

Discussion

It is now becoming increasingly clear that the development of all types of osteoarthritis
involves multiple etiological factors. Meniscus injuries, misaligned fractures and
post-traumatic articular cartilage surface defects are important causes of premature,
localized osteoarthritis of the knee. The risk of developing posttraumatic knee osteoarthritis
is increased more than threefold following major knee injury [31]. The local biomechanical risk factors which determine the site and severity of the
KOA include injury, obesity, anatomical deformity and muscle weakness [32].

Guidelines from the European League against Rheumatism (EULAR) state that both pharmacological
and non-pharmacological interventions are needed for optimal treatment of knee osteoarthritis
[33]. The various potentially effective pharmacological interventions at the clinicians'
disposal [33] highlight the need for information regarding treatment efficacy. The recent introduction
of coxibs seemed to promise a reduction in serious adverse events related to NSAIDs,
but this remains controversial [33]. As the evidence on the role of dietary factors in rheumatic disorders grows, it
becomes increasingly important for clinicians and investigators in the field of rheumatology
to familiarize them with the relevant data and appropriately apply them to clinical
and public health practice.

The efficacy of G. kola, naproxen and celebrex was apparent for the KOA patients within the six weeks of
therapy. G. kola's onset of action was relatively fast with better improvement when compared with
the placebo. The Garcinia kola positive analgesic/anti-inflammatory effect [8,9] were significant in KOA patients. This may be a useful alternative in patients with
osteoarthritis who have not responded to first-line treatment with acetaminophen and
in whom non steroidal anti-inflammatory drugs are contraindicated, ineffective, or
poorly tolerated. As serious adverse effects are associated with oral NSAIDs, only
limited use can be recommended [13].

G. kola is known to contain high content of bioflavonoid compounds [17] with a general anecdotal effect in folk medicine in Africa [15]. Active oxygen and free radicals are related to various physiological and pathological
events, such as inflammation [34]. There is always a relationship between oxidation, infections, inflammatory reactions,
and biological membrane of cells [18]. It has been reported to prevent accumulation of lipid per oxidation products and
protect biomembranes against oxidative damage by acting as antioxidant [14]. It also acts as scavenger of free radicals and reactive oxygen species [19] which are not treated by traditional NSAIDs drugs or selective COX-2 inhibitors.
When free radicals and reactive oxygen species accumulate in the joint could trigger
additional inflammatory processes in KOA. The scavenging activity of flavonoids of
G. kola seeds on super oxide anion radicals (O2) generated non-enzymically was comparable with butylated hydroxytoluene [15]. The reducing power shows that flavonoids of G. kola seeds are electron donors and could react with free radicals to convert them to stable
products thereby terminating radical chain reaction [35] involved in knee osteoarthritis inflammatory process.

Garcinia kola may be acting as antioxidant to either inhibit or slow down the progression of symptomatic
knee osteoarthritis. It could also act as a scavenger to remove the particles that
have been observed on the surfaces of human articular cartilage following trauma and
osteoarthritis [35]. The particles contained calcium and phosphorus which were identified only in structurally
abnormal cartilage [35]. Bitter kola has been known to protect against the oxidation of lipoprotein, presumably
through the mechanisms involving metal chelating and antioxidant activity [19,36]. The relief of pain experienced by subjects on G. kola could be associated with either removal of the free radicals and or revascularization
of the subchondria bone through the anti-atherogenic effect. This pathway is not clear
at this stage of the study. It may be through activation of the cytokines selective
inhibition of inducible nitric oxide synthase which has been shown to reduce the progression
of experimental osteoarthritis in vivo [37].

The bitter kola is believed to have aphrodisiac properties [15] probably related to its vasodilator effects on the genitalia smooth muscles. Reduction
of intraosseous/subchondria pressures could be the other pathway for the reduction
of knee pain experienced by patients on G. kola. The ability to lower intraocular pressure was earlier noted in glaucoma patients.
The preliminary crude observation was confirmed scientifically in animals and human
glaucoma's patients [38]. The vasodilatation induced could improve the subchondria blood circulation in knee
osteoarthritis. The G. kola extract has been shown to have antithrombotic activities [20]. The effect of G. kola on chondrocyte nutrition is not clearly elucidated at present. This will form the
fulcrum of future studies.

Conclusion

Garcinia kola clinically appeared to have a significant analgesic/anti-inflammatory effects in knee
osteoarthritis patients. G. kola is a potential osteoarthritis disease modifier. This study shows that G. kola is effective in improving locomotors function and significant pain reduction in patients
with knee OA. Further study is required for standardization of dosages of G. kola in KOA.

Authors' contributions

AOO conceived of the study, participated in its design and coordination and manuscript
writing. ASA actively involved in the study design and coordination and manuscript
writing. TOI characterized the chemistry of G Kola and participated in study coordination.
OCO participated in the design and study coordination. OAO involved in the design
and study coordination. EOI was involved in the study design and coordination. All
authors read and approved the final manuscript.

Acknowledgements

Funding: Dr. O O Adegbehingbe and all members of this study have not received grants or research
support from any corporation. AOO has also not been on the speakers bureaus of any
company. There are no predetermined legal gains or competing commercial interests
attached to this study.

We expressed our appreciation to Dr Owotade FJK (FWACS) and Dr Sowande AA (FRCS, FWACS)
for their time to proof read this manuscript. Also, Mr. Bisiriyu Luqman (M.Sc) deserved
thank you from us for the statistical analysis of the data.